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Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1.

TitleSimulative and experimental investigation on the cleavage site that generates the soluble human LOX-1.
Publication TypeJournal Article
Year of Publication2013
AuthorsBiocca, S, Arcangeli, T, Tagliaferri, E, Testa, B, Vindigni, G, Oteri, F, Giorgi, A, Iacovelli, F, Novelli, G, Desideri, A, Falconi, M
JournalArch Biochem Biophys
Volume540
Issue1-2
Pagination9-18
Date Published2013 Dec
ISSN1096-0384
KeywordsAmino Acid Motifs, Amino Acid Sequence, Humans, Hydrogen Bonding, Mass Spectrometry, Models, Molecular, Molecular Sequence Data, Protein Stability, Protein Structure, Tertiary, Proteolysis, Reproducibility of Results, Scavenger Receptors, Class E, Solubility, Solvents, Static Electricity, Surface Properties
Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that mediates the recognition, the binding and internalization of ox-LDL. A truncated soluble form of LOX-1 (sLOX-1) has been identified that, at elevated levels, has been associated to acute coronary syndrome. Human sLOX-1 is the extracellular part of membrane LOX-1 which is cleaved in the NECK domain with a mechanism that has not yet been identified. Purification of human sLOX-1 has been carried out to experimentally identify the cleavage site region within the NECK domain. Molecular modelling and classical molecular dynamics simulation techniques have been used to characterize the structural and dynamical properties of the LOX-1 NECK domain in the presence and absence of the CTLD recognition region, taking into account the obtained proteolysis results. The simulative data indicate that the NECK domain is stabilized by the coiled-coil heptad repeat motif along the simulations, shows a definite flexibility pattern and is characterized by specific electrostatic potentials. The detection of a mobile inter-helix space suggests an explanation for the in vivo susceptibility of the NECK domain to the proteolytic cleavage, validating the assumption that the NECK domain sequence is composed of a coiled-coil motif destabilized in specific regions of functional significance.

DOI10.1016/j.abb.2013.10.001
Alternate JournalArch. Biochem. Biophys.
PubMed ID24113299